Myelography is a valuable diagnostic tool for disorders of the spinal canal. Water soluble radiopaque contrast media (CM) must be injected at concentrations from .4 to 1 M in order to produce adequate opacification. A new generation of nonionic CM have significantly reduced reactions to myelography, however, reactions are still common and our knowledge of the mechanisms involved is far from complete. The objective of this work is to identify the mechanisms involved in toxicity and to differentiate the dependence of toxicity on specific and generic CM properties. We and others have demonstrated that some CM cause significant metabolic disturbances. This effect does not appear to involve competition for the membrane glucose carrier. In the proposed work we will determine if the metabolic disturbance is a nonspecific effect on the carrier or if the CM is disturbing other cell functions which effect metabolism. Our preliminary data indicate that several of the CM have effects on electrolyte and neurotransmitter fluxes. In addition the dilution of CSF by the spinal injections of nonionic CM can disrupt electrolyte balance. In the proposed work we will quantify the disturbances in CSF composition and we will examine the distribution of CM in spinal cord and brain tissue. The effects measured will be correlated to the properties of the specific CM molecules examined. The experiments will involve in vivo rabbit models together will well established brain slice, cell culture and synaptosome models. The information available indicates substantial differences in the new CM, as well as possible further methods to reduce toxicity.